Relationship of common variants in Interleukin 33 gene with susceptibility and prognosis of osteosarcoma in Han Chinese population

Kang, Chao; Zhao, Jianwu; Wang, Yuanchun; Yang, Chenguang; Chen, Jie; Zhi, Liqiang

doi:10.7150/jca.29086

Cited by 6 publications

(5 citation statements)

References 39 publications

(41 reference statements)

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“…Also, IL-33 gene polymorphisms were reported to be correlated with an increased risk of osteosarcoma [19]. IL-33 has been identified as a potential risk factor for the development and prognosis of osteosarcoma [20]. However, the role of IL-33 in human osteosarcoma cells remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

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The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway

Wang

Zhao

et al. 2020

Med Sci Monit

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Background:Osteosarcoma is the most common primary tumor of bone. Interleukin-33 (IL-33) is a pro-inflammatory cytokine that also participates in tumor progression. This study aimed to investigate the role of IL-33 in human osteosarcoma cell viability, proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) in vitro and the molecular mechanisms involved. Material/Methods:The normal osteoblast cell line, hFOB 1.19, and the human osteosarcoma cell lines SOSP-9607, SAOS2, MG63, and U2OS were studied. The expression of IL-33 mRNA and protein in human osteosarcoma cell lines were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot, respectively. The effects of IL-33 on human osteosarcoma cell viability, apoptosis, EMT, and the signaling pathways were studied using the MTT assay, flow cytometry, qRT-PCR, and Western blot. Results:IL-33 was upregulated in human osteosarcoma cell lines, including U2OS cells. The use of an IL-33 gene plasmid promoted osteosarcoma cell viability, inhibited cell apoptosis, increased the expression of Bcl-2, and reduced the expression of Bax. IL-33 reduced the level of E-cadherin and increased the levels of N-cadherin and matrix metalloproteinase-9 (MMP-9) in osteosarcoma cells at the mRNA and protein level. The use of the IL-33 plasmid increased the protein expression levels of p-AKT and the p-AKT/AKT ratio in osteosarcoma cells, and IL-33 siRNA reversed these findings. Conclusions:IL-33 was highly expressed in human osteosarcoma cells. Down-regulation of IL-33 reduced cell viability and EMT of osteosarcoma cells, and induced cell apoptosis through activation of the PI3K/AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…These findings indicate that IL-33 may promote tumor progression. However, although IL-33 has previously been reported to be expressed in osteosarcoma [18][19][20], the role and mechanisms of IL-33 in osteosarcoma cells remain unclear.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway

Wang

Zhao

et al. 2020

Med Sci Monit

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“…Multiple SNPs were located within ATAC-Seq peaks in the 1A1-1B intron region that correspond to putative enhancers (dashed boxes, including rs72614080, rs16924159, rs16924161, and rs12551256). Among these, rs72614080 is associated with prognosis in osteosarcoma ( 45 ), rs16924159 with vascular disease ( 46 ), and an off-peak SNP rs1891385 with COPD ( 47 ). Other SNPs associated with airway disease ( 42 ) are located ~6 kb proximal to the A2 promoter (rs992969 and rs3939286) and do not correspond to ATAC-Seq peaks observed in this data set; however, an AP-1 binding site was reported within the region encompassing these SNPs.…”

Section: Resultsmentioning

confidence: 99%

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease

Raphael,

Hassan,

Osorio

et al. 2024

JCI Insight

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IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 ( TFAP2A , TFAP2C ) and AP-1 ( FOS and JUN ) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD.

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“…Noteworthy, the TT genotype of this variant was not related to GLDC expression, but it was associated to lower expression of interleukin-33 (IL33) (40,76). On top of that, Kang and colleagues genotyped common variants in the IL33 gene and found that the A-allele of rs1048274 was associated to survival in a osteosarcoma patient cohort of Chinese ancestry (77). The patient cohort of Koster et al consisted of European and Brazilian subjects and they did not identify statistically signi cant associations with common variants in IL33.…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review of 2010-2020

Hurkmans

Brand²,

Verdonschot

et al. 2022

Preprint

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Background: Osteosarcoma is the most common bone tumor in children and adolescents. Despite multiagent chemotherapy, only 71% of patients survives and these survivors often experience long-term toxicities. The main objective of this systematic review is to provide an overview of the discovery of novel associations of germline polymorphisms with treatment response and/or chemotherapy-induced toxicities in osteosarcoma.Methods: MEDLINE and Embase were systematically searched (2010-2020). Genetic association studies were included if they assessed >10 germline genetic variants in > 5 genes in relevant drug pathways or if they used a genotyping array or other large-scale genetic analysis. Quality was assessed using adjusted STrengthening the REporting of Genetic Association studies (STREGA)-guidelines. To find additional evidence for the identified associations, literature was searched to identify replication studies.Results: After screening 1533 articles, fifteen articles met our inclusion criteria. These range from studies focusing on genes in relevant pharmacokinetic pathways to whole genome sequencing. Eight articles reported on doxorubicin-induced cardiomyopathy. For seven genetic variants in CELF4, GPR35, HAS3, RARG, SLC22A17, SLC22A7 and SLC28A3, replication studies were performed, however without consistent results. Four small studies reported on bone marrow, nephro- and/or hepatotoxicity. Six studies included analysis for treatment efficacy. Genetic variants in ABCC3, ABCC5, FasL, GLDC, GSTP1 were replicated in studies using heterogeneous efficacy outcomes.Conclusions: Despite that results are promising, the majority of associations were poorly reproducible due to small patient cohorts. For the future, hypothesis-generating studies in large patient cohorts will be necessary, especially for cisplatin-induced ototoxicity as these are lacking. In order to form large patient cohorts, national and international collaboration will be essential.

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Relationship of common variants in Interleukin 33 gene with susceptibility and prognosis of osteosarcoma in Han Chinese population

Cited by 6 publications

References 39 publications

The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway

The Effects of Interleukin-33 (IL-33) on Osteosarcoma Cell Viability, Apoptosis, and Epithelial-Mesenchymal Transition are Mediated Through the PI3K/AKT Pathway

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease

Pharmacogenetics of chemotherapy treatment response and -toxicities in patients with osteosarcoma: a systematic review of 2010-2020

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